Adolescent preconceptional smoking alters the body weight of the next generation in a sex-specific manner

Introduction: A recent multicenter epidemiological study suggested that paternal smoking during adolescence can increase the risk to develop early-onset non-allergic asthma in children. The effects on offspring were still observed even when fathers had quit smoking years before the child was born. However, the underlying mechanisms are currently unexplored. Therefore we aimed to develop a murine model of adolescent smoking in order to investigate the parental and offspring´s phenotype.Methods: Male and female C57BL/6 mice (21-day-old) were exposed to mainstream cigarette smoke (CS) (research cigarettes 3R4F, University of Kentucky) for 2 weeks to 1puff/min (6 cigarettes) and 4 weeks to 4puffs/min (24 cigarettes) for 1 hour per day for 5 days/week. Thereafter, CS-exposed animals were mated with air-controls. The body weight of offspring was recorded daily.Results: CS-exposed male and female parents showed a decrease in weight gain compared to air-controls. 50% of control females became pregnant in comparison to only 25% of pregnant females in the CS-exposed group, where sperm counts, sperm morphology and spermatogonia count were normal in males. CS-exposed fathers showed elevated macrophages and neutrophilia in BAL. Male offspring from smoking fathers demonstrated an increase in body weight on PND2 and PND3, whereas female offspring's body weight was normal. Male and female offspring from smoking mothers had a lower body weight compared to non-smoker offspring. Using Next-Generation Sequencing, we found the abundance of some miRNA transcripts to be altered in sperm of smoking parents.Conclusion: Despite normal sperm count and morphology, we observed a decrease in pregnancy rate in adolescent smoking mothers. In offspring, we were able to detect an altered body weight in offspring from adolescent smoking fathers and mothers, following sex-specific patterns.